Research Review: Change your DNA with exercise

By Helen Kollias

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Over the years we’ve been hearing a lot about genetics and DNA.

Wide hips? It’s your genes.

Sweet tooth? Damn genes again!

DNA seems to be this unchanging and uncompromising molecule that ties you to your fate. You can’t change your fate nor can you change your DNA… or so the message goes. But you can change your DNA — or at least what parts are used (or not).

What DNA you have vs. what your DNA does

Back in high school biology, you probably learned that DNA is your genetic code — the cellular instructions to make proteins.

It seems like DNA is in control of what happens to you. To some degree, that’s true. But when, which part, and how much of your DNA is being used at any given time is just as important as what your DNA is coding.

Without going into all the other ways of controlling DNA decoding (it’s called transcription and translation when you make proteins from DNA via RNA) there are things that change your DNA. You’re not necessarily “stuck with” your genes.

Your body turns DNA off and on all the time. Otherwise you’d be one nebulous type of cell — no skin cells, no heart cells, no bone cells, no brain; just a blob of undifferentiated goo. Obviously that doesn’t happen. You have skin, a heart, bones, and a brain. How can that be? All these cells have the same DNA… but do different things.

Thus: having a particular kind of DNA is different from what DNA does. Research on this turning-off and turning-on, as well as the decision about which bits of DNA are involved, is a new field of study known as epigenetics.

How to control your DNA

There are a few ways of controlling DNA expression without changing the actual DNA.

One cool thing about these types of modifications: they can be passed on to the next generation, so that some types of changes that happen in the parents eggs/sperm will be passed on to their children. Again, this area of inheritance is called epigenetics, since it happens outside traditional genetic inheritance.

Histone modifications

RNA-mediated phenomena

RNA isn’t only the intermediary code from DNA to protein. It can do a lot of other things, like interfering with DNA codes (called interference RNA or RNAi).

DNA methylation & promoters

DNA methylation is the best understood way of controlling DNA and is pretty straightforward. While most people understand DNA as being about genes, there are other parts of DNA that aren’t genes, and don’t code for proteins. Those parts are called promoters.

Promoters either promote or repress the decoding of a nearby gene (DNA) into RNA that then makes the protein (no RNA = no protein). That makes sense. You don’t want to constantly make proteins from every gene in all cells. If you block promoters from functioning, then you can’t make protein from that gene. Kinda like blocking your Aunt Bertha from getting into the kitchen to make her famous haggis stroganoff.

DNA methylation is one way to block promoters from working. For a long time, scientists figured that this took a while to happen — say, weeks, months, or even years. In fact, the environment can change methylation more quickly than we expected. I’ll get to that in a bit.

DNA methylation is a chemical reaction that puts a methyl group onto DNA. All you need to know is that the process blocks promoters from turning on genes to make proteins. More methylation means less gene activation, and fewer proteins (Figure 1).

Research is showing that methylation is an important process in genetic health. For instance, if genetic expression isn’t well regulated, you can have all kinds of unwanted stuff popping up — which is the hallmark of diseases like cancer. You don’t want too much or too little methylation. You want it to be well organized and controlled, and you want all your genes and proteins doing their jobs properly.[1]

Methods

This study used people, animals, and cells in petri dishes (aka in vitro). Obviously, using whole people is the best thing to use (since we are whole people), but if you want to tease out different parts you need to use isolated muscle or individual cells. This is where the petri dish stuff comes in handy.

Whole-body exercise

First, researchers had healthy young men bike until they were exhausted in order to figure out their VO2peak (a way of measuring how much oxygen they could use). Then, they had the men exercise at low intensity (40% VO2peak) and high intensity (80% VO2peak).

After each exercise session the researchers took a muscle sample from the volunteers.

Single-muscle contraction

To figure out if it’s the muscle contraction during exercise that causes the change in DNA methylation, researchers took the soleus muscle from a rat and used electrodes (similar to Dr. Ho’s late-night infomercial apparatus) to get the muscle to contract.

Single-cell exercise trigger

Other cellular changes like the energy state of the cell (AMP:ATP ratio) and intracellular redox state of the cell could also be involved in methylation.

In the third step, researchers mimicked exercise-triggered changes using a single cell and caffeine. Caffeine triggers release of calcium stored in a subcellular part of the cell (sarcoplasmic reticulum). Since calcium released goes on to trigger the contraction (actin-myosin cross-bridge cycling), it could be what triggers changes in methylation.

To make sure it wasn’t the caffeine itself causing changes, the researchers set up a second experimental condition with caffeine plus a blocker of calcium release from the sarcoplasmic reticulum (dantrolene); and a third condition with a chemical that pokes holes into the sarcoplasmic reticulum (ionomycin) so that calcium is released without caffeine.

Results

Exercise changes methylation

After biking to max aerobic capacity (during a VO2peak testing ) muscle samples were taken from each volunteer’s thigh 20 minutes after exercise.

Muscle samples showed more mRNA and proteins of genes that are part of fuel (fat, carbohydrate) utilization and mitochondrial function. That means that the body is adapting to the first round of exercise by making more protein and cell structures to deal with the next round of possible exercise.

By having more proteins involved in using fuel, you’ll be able to use the fuel faster and more effectively. And with higher-functioning mitochondria, you’ll be able to use oxygen better and convert fuel to more energy (more ATP).

Finding that there’s more mRNA and proteins after exercise isn’t new; what is new is that methylation is one way of controlling the process of making more mRNA.

What these researches found was that exercise changed how much methylation was on DNA in general (global DNA methylation) and on specific genes that respond to exercise.

They found that there was less methylation (hypomethylation) after exercise. That means that overall, genes were more likely to be made into proteins.

Two groups of genes responded:

genes that make proteins for exercise — think worker bees

genes that make proteins that control other proteins and genes — think CEOs or queen bees

Small changes in CEO proteins (transcription factors) cause big changes in worker bee proteins, so you may not see much of a change in CEO protein, but still get changes in worker bee proteins.

After exercise, there was less methylation in genes that make worker bee proteins. This means there would be more worker bee proteins made, but no change in methylation of the genes that make CEO proteins.

Exercise intensity and genes

To figure out if exercise intensity was important to change DNA methylation, the researchers set up a simple experiment comparing aerobic low and high intensity biking. Since we already know that more intense aerobic exercise increases the production of key genes, researchers wanted to figure out whether there was less DNA methylation on these genes after exercise.

There was no difference in methylation after low intensity exercise, but right after high intensity exercise there was less methylation in the promoter region of genes key in responding to exercise:

PGC-1α

TFAM

MEF2A

PDK4

Three hours after exercise, PPAR-δ had less methylation in its promoter region. Less methylation related to more of that gene’s RNA being made.

Muscle contraction changes methylation

Next step was to stimulate muscle contraction in a single muscle cell — again, a rat soleus.

After a total of 60 minutes of stimulation and 180 minutes of recovery, there were increases in mRNA of key genes (PGC-1α, PPAR-δ, PDK4) that correlated with less methylation of the corresponding promoter after 45 minutes of rest. This decrease in methylation is likely one part of why there is more mRNA from that gene 3 hours later.

Calcium release changes methylation

After comparing all three conditions in the single-cell experiment, the researchers were fairly confident that calcium somehow increased exercise-responding gene expression and decreased the methylation of the promoter region of those same genes.

However, calcium alone is not enough to modify methylation, since caffeine decreased methylation more than poking hole in the sarcoplasmic reticulum.

Conclusion

Exercise can change your DNA or least whether it will decode to make protein.

Until this study was done, scientists thought that modifying DNA without changing the code (i.e., epigenetic changes) required long term exposure to specific foods or environments. This study found that — surprisingly — one bout of exercise was enough to change DNA methylation.

Exercise decreased methylation both in specific genes known to respond to exercise, and also more generally across all DNA. Less methylation means more genes making proteins.

The researchers figure that calcium is a big player in how DNA methylation goes down, but there is still more to learn.

Bottom line

A common saying in the field of genetics is “Genes load the gun; environment pulls the trigger.”

We often assume that our DNA determines how our body responds… but you can also do things that change the expression of that DNA.

In this study, even a brief round of high-intensity exercise was enough to change DNA. Now, just imagine what a good workout routine could do!